It is proposed to undertake a study of some possible biochemical bases for the behavioral abnormalities observed in patients in renal failure. In view of the fact that Ca2+ is an intracellular second messenger in the nervous system, and that abnormalities of Ca2+ metabolism in brain and other tissues have been observed in patients suffering from renal failure, we propose to study the protein substrates for Ca2+/calmodulin-dependent protein kinases in the brain, as well as certain other parameters of brain calmodulin biochemistry. The study of the protein substrates for Ca2+/calmodulin-dependent protein kinases will include the purification and characterization of these substrates, development of radioimmunoassay procedures for determining their absolute amounts, and study of the Ca2+-dependent phosphorylation of these endogenous substrates in intact brain slices in response to depolarizing agents. We shall also undertake a study of the amount and distribution of calmodulin, attempt to detect as many calmodulin-binding proteins as possible in the mammalian brain and to carry out the purification and characterization of those calmodulin-binding proteins that are associated with systems other than protein phosphorylation. In all of these studies, we shall compare the amount of the individual substances in the brains of normal rats and rats used as models of chronic renal insufficiency.